Toxicity of desoxycorticosterone pivalate given at high dosages to clinically normal Beagles for six months

Edward Chow From the Agricultural Division, Environmental Health Center, Ciba-Geigy Corp, 400 Farmington Ave, Farmington, CT 06032, and the Agricultural Division, Ciba-Geigy Animal Health, Box 18300, Greensboro, NC 27419.

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William R. Campbell From the Agricultural Division, Environmental Health Center, Ciba-Geigy Corp, 400 Farmington Ave, Farmington, CT 06032, and the Agricultural Division, Ciba-Geigy Animal Health, Box 18300, Greensboro, NC 27419.

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John C. Turnier From the Agricultural Division, Environmental Health Center, Ciba-Geigy Corp, 400 Farmington Ave, Farmington, CT 06032, and the Agricultural Division, Ciba-Geigy Animal Health, Box 18300, Greensboro, NC 27419.

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Randy C. Lynn From the Agricultural Division, Environmental Health Center, Ciba-Geigy Corp, 400 Farmington Ave, Farmington, CT 06032, and the Agricultural Division, Ciba-Geigy Animal Health, Box 18300, Greensboro, NC 27419.

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Kenneth L. Pavkov From the Agricultural Division, Environmental Health Center, Ciba-Geigy Corp, 400 Farmington Ave, Farmington, CT 06032, and the Agricultural Division, Ciba-Geigy Animal Health, Box 18300, Greensboro, NC 27419.

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Summary

Desoxycorticosterone pivalate was administered im to juvenile Beagles at 0, 2.2, 6.6, or 11 mg/kg of body weight daily over a consecutive 3-day period every 28 days (equivalent to a cumulative monthly dosage of 0, 6.6, 19.8, or 33 mg/kg) for 6 months. Polyuria, polydipsia, and decreases in serum potassium and bun concentrations were detected while the dogs were being treated. Transient increases in serum sodium concentrations also were detected. The treated males had significant decreases in body weight gain, resulting in an 18% decrease in body weight in the 11-mg/kg dosage group, compared with the controls. The weights of the adrenal glands, epididymides, and testes also were lower in the treated males. Organ weights for the 2.2, 6.6, and 11-mg/kg dosage groups were: 86, 79, and 69%, respectively, of the controls (adrenal glands); 80, 70, and 68%, respectively, of the controls (epididymides); and, 79, 75, and 67%, respectively, of the controls (testes). When normalized to body weight, these decreases in organ weight were still dosage-dependent, but the differences were less remarkable. In contrast, the relative weight (to body weight) of the kidneys (males and females) and of the thyroid and parathyroid glands (males) were higher dosage-dependently. All of the treatment-related effects, other than organ and body weight changes, appeared to be reversible following the cessation of treatment. On the basis of these results, it was concluded that treatment with desoxycorticosterone pivalate could be tolerated, even when given at dosages 15-fold the therapeutic dosage of 2.2 mg/kg every 25 days.

Summary

Desoxycorticosterone pivalate was administered im to juvenile Beagles at 0, 2.2, 6.6, or 11 mg/kg of body weight daily over a consecutive 3-day period every 28 days (equivalent to a cumulative monthly dosage of 0, 6.6, 19.8, or 33 mg/kg) for 6 months. Polyuria, polydipsia, and decreases in serum potassium and bun concentrations were detected while the dogs were being treated. Transient increases in serum sodium concentrations also were detected. The treated males had significant decreases in body weight gain, resulting in an 18% decrease in body weight in the 11-mg/kg dosage group, compared with the controls. The weights of the adrenal glands, epididymides, and testes also were lower in the treated males. Organ weights for the 2.2, 6.6, and 11-mg/kg dosage groups were: 86, 79, and 69%, respectively, of the controls (adrenal glands); 80, 70, and 68%, respectively, of the controls (epididymides); and, 79, 75, and 67%, respectively, of the controls (testes). When normalized to body weight, these decreases in organ weight were still dosage-dependent, but the differences were less remarkable. In contrast, the relative weight (to body weight) of the kidneys (males and females) and of the thyroid and parathyroid glands (males) were higher dosage-dependently. All of the treatment-related effects, other than organ and body weight changes, appeared to be reversible following the cessation of treatment. On the basis of these results, it was concluded that treatment with desoxycorticosterone pivalate could be tolerated, even when given at dosages 15-fold the therapeutic dosage of 2.2 mg/kg every 25 days.

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